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Wheat Chromatin Architecture Is Organized in Genome Territories and Transcription Factories Lorenzo Concia1, Alaguraj Veluchamy2, Juan S

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Wheat Chromatin Architecture Is Organized in Genome Territories and Transcription Factories Lorenzo Concia1, Alaguraj Veluchamy2, Juan S Concia et al. Genome Biology (2020) 21:104 https://doi.org/10.1186/s13059-020-01998-1 RESEARCH Open Access Wheat chromatin architecture is organized in genome territories and transcription factories Lorenzo Concia1, Alaguraj Veluchamy2, Juan S. Ramirez-Prado1, Azahara Martin-Ramirez3, Ying Huang1, Magali Perez1, Severine Domenichini1, Natalia Y. Rodriguez Granados1, Soonkap Kim2, Thomas Blein1, Susan Duncan4, Clement Pichot1, Deborah Manza-Mianza1, Caroline Juery5, Etienne Paux5, Graham Moore3, Heribert Hirt1,2, Catherine Bergounioux1, Martin Crespi1, Magdy M. Mahfouz2, Abdelhafid Bendahmane1, Chang Liu6, Anthony Hall4, Cécile Raynaud1, David Latrasse1 and Moussa Benhamed1,7* Abstract Background: Polyploidy is ubiquitous in eukaryotic plant and fungal lineages, and it leads to the co-existence of several copies of similar or related genomes in one nucleus. In plants, polyploidy is considered a major factor in successful domestication. However, polyploidy challenges chromosome folding architecture in the nucleus to establish functional structures. Results: We examine the hexaploid wheat nuclear architecture by integrating RNA-seq, ChIP-seq, ATAC-seq, Hi-C, and Hi-ChIP data. Our results highlight the presence of three levels of large-scale spatial organization: the arrangement into genome territories, the diametrical separation between facultative and constitutive heterochromatin, and the organization of RNA polymerase II around transcription factories. We demonstrate the micro-compartmentalization of transcriptionally active genes determined by physical interactions between genes with specific euchromatic histone modifications. Both intra- and interchromosomal RNA polymerase-associated contacts involve multiple genes displaying similar expression levels. Conclusions: Our results provide new insights into the physical chromosome organization of a polyploid genome, as well as on the relationship between epigenetic marks and chromosome conformation to determine a 3D spatial organization of gene expression, a key factor governing gene transcription in polyploids. Keywords: Hi-C, Hi-ChIP, DNA loops, Transcription factories, Genome territories * Correspondence: [email protected] 1Institute of Plant Sciences Paris of Saclay (IPS2), UMR 9213/UMR1403, CNRS, INRA, Orsay, France 7Institut Universitaire de France (IUF), Paris, France Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Concia et al. Genome Biology (2020) 21:104 Page 2 of 20 Background from the same (autopolyploid) or related (allopolyploidy) In eukaryotes, nuclear DNA is folded into chromatin, a species in the same nucleus. How polyploidy affects tightly packed high-order structure whose main compo- chromosome folding architecture and functional nents are DNA and histone proteins. Chromatin con- organization remains to be elucidated. Established poly- formation determines the accessibility of the double ploids often have higher fitness attributes [16], and poly- helix to the transcriptional and replication machineries ploidy is considered a major factor in successful plant [1]. It is tightly regulated in both time and space by domestication [17] as demonstrated by its widespread highly conserved mechanisms such as DNA methylation, presence among cultivated crops, both autopolyploids histone post-translational modifications, alterations in (e.g., potato [Solanum tuberosum], alfalfa [Medicago histone-DNA interactions, and incorporation of histone truncatula], banana [Musa acuminata], and watermelon variants by chromatin remodelers, as well as long non- [Citrullus lanatus]) and allopolyploids (e.g., canola, coding RNA (lncRNA)- and small RNA (sRNA)-related strawberry, cotton, coffee, sugarcane, and wheat) [18]. pathways [2–4]. Polyploidization events trigger extensive epigenetic In light of the strong influence of chromatin conform- and transcriptional alteration of the duplicated or ation on gene expression, the idea of the genome as a lin- merged genomes, accompanied by small- and large-scale ear sequence of nucleotides has been replaced by a conformational changes [18–23]. Such rearrangements dynamic three-dimensional (3D) architecture [5]inwhich are thought to have facilitated the domestication of poly- structural elements such as “loops”, “domains”, “territor- ploid crops by enhancing their adaptive plasticity [17]. ies”,and“factories” are functional components controlling The characterization of 3D chromosome topology in the physical interactions between promoters and distant polyploids crops may help better understand the degree regulatory elements [6]. Accordingly, the nucleus is to which spatial organization contributes to polyploidy thought to operate as an integrated regulatory network [7]. success. Recent development of new methods for the analysis Modern hexaploid wheat (Triticum aestivum L.; 2n = of the genome-wide 3D spatial structure of chromatin, 6x = 42) is a particularly interesting model for analyzing such as Hi-C, Hi-ChIP, and ChlA-PET, has made it pos- chromosome topology, because it is the product of two sible to unveil small- and large-scale genome topology in rounds of interspecific hybridization that occurred at various cell types of metazoan organisms, notably in different evolutionary times (Fig. 1a). The first mammals [8]. These studies revealed the existence of hybridization event occurred 0.36 to 0.50 million years megabase-long chromatin compartments comprising ei- ago and produced a tetraploid species, Triticum turgi- ther open, active chromatin (A compartment) or closed, dum (AABB) [24–27]. This hybridization involved Triti- inactive chromatin (B compartment). Chromatin con- cum urartu (donor of the AA genome) and an unknown formation capture techniques also allowed the descrip- species related to Aegilops speltoides (BB genome) [28]. tion of topologically associating domains (TADs), large Indeed Ae. speltoides cannot be considered as the exclu- chromatin domains (800 kb average length in mammals) sive donor of this genome, but the wheat B genome bringing together contiguous sequences of DNA. Genes might rather have a polyphyletic origin with multiple an- that belong to the same TAD display similar dynamics cestors involved, among which Ae. speltoides. A second of expression, suggesting that physical association is hybridization event between T. turgidum (AABB) and functionally relevant to gene expression control. the diploid species Aegilops tauschii (DD genome) gave The basic organization of plant genomes differs from rise to a hexaploid wheat (AABBDD), the ancestor of the that in animals [9–14]. For instance, plants do not dis- modern bread wheat, about 10,000 years ago [25, 29]. play an apparent A/B compartmentalization as a pre- Since the three ancestors are closely related species des- dominant genome folding feature [14, 15]. cended from a common progenitor, three distinct but Moreover, although TAD-like domains have been highly syntenic subgenomes can be identified (AA, BB, identified in maize, tomato, sorghum, foxtail millet, and and DD) [30]. Compared to tetraploid wheat, modern rice [15], no canonical insulator proteins have been de- hexaploid wheat possesses several agricultural advan- scribed in plants, challenging the classification of these tages, such as increased environmental adaptability, tol- structures [12]. This may be due to the fact that the erance to abiotic stresses (including salinity, acid pH, plant genome structure has a particular transposable and cold), and increased resistance to several pathogens, element content and location relative to genes and opens factors that contribute to its success as a crop [31]. Al- the question of the functional conservation of genome though the genetic determinants of wheat yield and folding in eukaryotes. quality have been extensively investigated [32, 33] and a Another particular feature of plant genomes is the fully annotated reference genome was recently generated high occurrence of polyploidy, which leads to the co- together with tissue-specific and developmental tran- existence of several copies of similar genomes deriving scriptomic co-expression networks [34], the influence of Concia et al. Genome Biology (2020) 21:104 Page 3 of 20 Fig. 1 Large-scale chromatin architecture analysis of hexaploid wheat. a Schematic representation of the relationships between wheat genomes, showing the polyploidization history of hexaploid wheat. b Hi-C contact matrix of the hexaploid wheat genome.
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